The proposed investigations are in the field of arginine and urea synthesis and regulation in mammals, and, in particular, in man. Work will be done on the purification and characterization of the enzymes of the urea cycle from human liver. The preparation of antibodies to these enzymes will be attempted in order to develop radioimmunoassays for the measurement of enzymic proteins in small amounts of crude tissue, such as can be obtained by needle biopsy. These assays would be useful in the diagnosis of congenital deficiencies of urea cycle enzymes, and would aid in the study of structure-function relationships in mutant enzymes. The long- and short-term regulation of arginine and urea synthesis will be studied by examining the effects of different dietary conditions and some pathological conditons on the level of urea cycle enzymes and other, closely related enzymes in rat liver and kidney, and on the level of urea cycle intermediates in rat liver in vivo and in isolated hepatocytes.